In the July 15, 2010, issue of Genes & Development, Yoon and colleagues (pp. 1507-1518) report that, in a siRNA knockdown survey of 6363 genes in mouse C2C12 cells, they discovered 150 genes that regulated mitochondrial biogenesis and bioenergetics. Many of these genes have been studied previously for their importance in regulating transcription, protein and nucleic acid modification, and signal transduction. Some notable examples include Brac1, Brac2, Pax4, Sin3A, Fyn, Fes, Map2k7, Map3k2, calmodulin 3, Camk1, Ube3a, and Wnt. Yoon and colleagues go on to validate their observations by extensively documenting the role of Wnt signaling in the regulation of mitochondrial function.